The goal of the Children's Hospital Boston CHRCDA Program is to develop pediatrician physician-scientists who are performing world-class research that will improve health care for children in this country and around the world. Our Scholars will be performing laboratory-based basic and translational research under the mentorship of outstanding scientists at Children's Hospital and other Harvard Associated Hospitals and Harvard Medical School. Our program has been established to ensure the development of independent scientists. In this proposal we describe a program that included intensive mentoring, a comprehensive didactic program, and a program to ensure the scientific development of Scholars. Programmatic oversight will be provided by an External Site Visit Committee and an Internal Steering Committee. Plans are in place for programmatic self-evaluation and for review of Scholar Progress. We propose to continue the funding of four Scholar positions. Most Scholars will be funded for two years, unless they secure independent K-level or other funding during their first year of Scholarship. Historically, the Department of Medicine has funded the majority of the salary component of each Scholar, such that most of the K12 funding is used to cover the cost of supplies and research technicians. The Department has also in most years funded a position to support a fifth Scholar position. Scholars will be faculty members most often at the rank of Instructor, but Assistant Professors who are early in the development of their independent careers will also be eligible to apply. Scholars will be considered at any point from the beginning of their Instructorship to the point where they are considered to be two years away from submitting their first R-level NIH grant or equivalent. Scholars will work in a broad range of scientific investigations. Past and present Scholars are working in areas such as the mechanism of nuclear reprogramming, structural biology of malaria antigens, biochemistry of viral entry, gene discovery in short stature, cardiac malformations, focal segmental glomerulosclerosis and familial epilepsy, T cell development and many other areas. These investigations will elucidate fundamental molecular mechanisms and will lead to the development of new therapeutic modalities in all areas of pediatric disease, including hematology/oncology, endocrinology, nephrology, infectious disease, immunology, pulmonology and neurology. PUBLIC HEALTH RELEVANCE: The Department of Medicine at Children's Hospital Boston is dedicated to the training of physician-scientists and in helping them to develop careers as world- class independent scientists. We have a strong history of producing physician- scientists who have contributed to major discoveries in fundamental basic research and translational research that have had lasting impact on the treatment of pediatric disease. The Child Health Research Career Development Awards have played an integral role in supporting the development of physician-scientists at our institution and we propose to continue and strengthen this program over the next five years.